Fluticasone Propionate Pharmacogenetics: CYP3A4*22 Polymorphism and Pediatric Asthma Control

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• 作者：Chris Stockmann ; MSc¹ ; ² ; Bernhard Fassl ; MD¹ ; Roger Gaedigk ; PhD³ ; Flory Nkoy ; MD ; MPH ; MS¹ ; Derek A. Uchida ; MD¹ ; Steven Monson ; BS¹ ; Christopher A. Reilly ; PhD² ; J. Steven Leeder ; PharmD ; PhD³ ; Garold S. Yost ; PhD² ; Robert M. Ward ; MD¹ ; ² ; ^{Robert.Ward@hsc.utah.edu}
• 关键词：FP ; Fluticasone propionate ; HWE ; Hardy-Weinberg equilibrium ; SNP ; Single nucleotide polymorphism
• 刊名：The Journal of Pediatrics
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：162
• 期：6
• 页码：1222-1227.e2
• 全文大小：560 K

文摘

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class=""h4"">Objective

To determine the relationship between allelic variations in genes involved in fluticasone propionate (FP) metabolism and asthma control among children with asthma managed with inhaled FP.

class=""h4"">Study design

The relationship between variability in asthma control scores and genetic variation in drug metabolism was assessed by genotyping 9 single nucleotide polymorphisms in the CYP3A4, CYP3A5, and CYP3A7 genes. Genotype information was compared with asthma control scores (0 = well controlled to 15 = poorly controlled), determined using a questionnaire modified from the National Heart Lung and Blood Institute's Expert Panel 3 guidelines.

class=""h4"">Results

Our study cohort comprised 734 children with asthma (mean age, 8.8 ¡À 4.3 years) and was predominantly male (61 % ) and non-Hispanic white (53 % ). More than one-half of the children (56 % ; n = 413) were receiving an inhaled glucocorticoid daily, with FP the most frequently prescribed agent (65 % ). Among the children receiving daily FP, single nucleotide polymorphisms in CYP3A5 and CYP3A7 were not associated with asthma control scores. In contrast, asthma control scores were significantly improved in the 20 children (7 % ) with the CYP3A4*22 allele (median, 3; range, 0-6) compared with the 201 children without the CYP3A4*22 allele (median, 4; range, 0-15; P = .02). The presence of CYP3A4*22 was associated with improved asthma control scores by 2.1 points (95 % CI, 0.5-3.8).

class=""h4"">Conclusion

The presence of CYP3A4*22, which is associated with decreased hepatic CYP3A4 expression and activity, was accompanied by improved asthma control in the FP-treated children. Decreased CYP3A4 activity may improve asthma control with inhaled FP.